This application is for the continuing support of a multicategorical General Clinical Research Center consisting of a 21-bed patient unit and supporting Core Laboratory. The facility is available to the departments of the medical school for the pursuit of clinical research protocols. Clinical investigations to be supported by this grant include cardiovascular studies consisting of the delineation of the natural history of coronary artery disease, mechanisms of ischemic induced electrical instability, effects of vasodilator therapy and evaluation of coronary bypass surgery and the effects of antiarrhythmic agents. Studies of hereditary disorders including polyposis coli, homocystinuria and familial cryoglobulinemia as well as characterization of abnormal fetal hemoglobin synthesis, hemorrhagic disorders, and factors affecting red blood cell oxygen transport will also be pursued. Surgical evaluation of the effects of pancreatic tissue transplantation on diabetes mellitus and endocrine investigation on the effects of central opioids on ovulation will be carried out. Studies are also continuing on medullary-thyroid carcinoma. The effect of Crohn's disease on nitrogen metabolism and growth and of steroids on alcoholic hepatitis will be evaluated. A large number of protocols are designed to study the chronic uremic state and the effects of alpha ketoanalogue supplementation on the course of chronic renal failure. Alpha ketoanalogues will also be evaluated on the therapy of hyperammonemia secondary to portal system encephalopathy. Characterization of the renin-angiotensin system in diabetic renal failure, hypertension and edematous patients will continue to be studied.